DESCRIPTION: This proposal is to investigate the roles of the JNK cascade in TNF-alpha-induced apoptosis in vitro cell culture systems. This research is based on a publication report that TNF-alpha-induced apoptosis can be blocked by the dominant negative mutants of c-Jun and JNKK. The specific aims of this proposal are: 1) to investigate the effect of FADD on the JNK cascade in TNF-alpha-induced apoptosis, 2) to investigate the effect of selective inhibition of the JNK cascade on TNF-alpha-induced apoptosis, and 3) to investigate the effect of selective activation of the JNK cascade on TNF-alpha-induced apoptosis.